Registration Dossier

Administrative data

Description of key information

Exposure-based waiving: Repeated-dose toxicity testing has not been performed, because no significant exposure occurs in all scenarios of manufacture and identified uses.
In a worst case scenario a very conservative oral DNEL based on the TTC concept for chronic toxicity was choosen for MBTester, a Cramer class III substance (high hazard).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

According to the REACH Regulation, Annex XI.3 Substance-tailored exposure-driven testing. 3.1 Testing in accordance with Sections 8.6 and 8.7 of Annex VIII and in accordance with Annex IX and Annex X may be omitted, based on the exposure scenario(s) developed in the Chemical Safety Report.

3.2. (a) The manufacturer or importer demonstrates and documents that all of the following conditions are fulfilled:

(i) the results of the exposure assessment covering all relevant exposures throughout the life cycle of the substance demonstrate the absence of or no significant exposure in all scenarios of the manufacture and all identified uses as referred to in Annex VI Section 3.5.

The results of the exposure assessment are described in the CSR chapter 9 and 10. No significant exposure in all scenarios of the manufacture and all identified uses were identified.

(ii), a DNEL or a PNEC can be derived from results of available test data for the substance concerned taking full account of the increased uncertainty resulting from the omission of the information requirement, and that DNEL or PNEC is relevant and appropriate both to the information requirement to be omitted and for risk assessment purposes; (iii) the comparison of the derived DNEL or PNEC with the results of the exposure assessment shows that exposures are always well below the derived DNEL or PNEC.

Due to the identified uses exposure to the environment can be excluded.

As a basis for exposure-based waiving, the TTC concept as devised by Munro et al. [1, 2] is applied. MBTester is predicted to fall within Cramer Class III (high hazard). Within Cramer class III, the 5th-percentile NOEL has been identified from chronic oral studies or other oral studies e.g., developmental toxicity, if they were more sensitive. The majority of NOELs were defined by studies in the rat.

The generic oral NOEL applicable to MBTester (Class III) is 0.15 mg/kg bw/day corresponding to a very low DNEL of 1.5 µg/kg bw/d.

 

[1] Munro, IC,Ford, RA, Kennepohl, E, Sprenger, JG (1996).Correlation of Structural Classwith No-Observed-Effect Levels: A Proposal for Establishing a Threshold of Concern. Food Chem. Toxicol. 34 829-867.

[2] Munro, IC, Kennepohl, E, Kroes, R (1999). A procedure for the safety evaluation of flavouring substances. Food and Chemical Toxicology 37, 207-232.

 

(iii) the comparison of the derived DNEL or PNEC with the results of the exposure assessment shows that exposure are always well below the derived DNEL or PNEC.

The exposure values are well below the derived DNEL or PNEC. Please refer to chapter 9 and 10 of the CSR.

Justification for classification or non-classification

No classification proposed. The potential routes of repeated exposure to humans can be considered as negligible.